Effects of Carboplatin in Combination with Hyperthermia on Cell Death in Retinoblastoma Cell Line

ABSTRACT

PURPOSE: The effect of environmental acidity on the induction of apoptosis by heat and carboplatin alone or combined was investigated. METHODS: Human retinoblastoma Y79 and WERI cells were treated with hyperthermia at 42.5degrees C for 1 hr and 25~50 mM carboplatin alone or combined with hyperthermia in pH 7.5 or pH 6.6 medium and the resultant apoptosis was assessed based on the flow cytometric determination of DNA content, DNA fragmentation, and PARP cleavage. The cell viability was alone determined with trypan blue exclusion method. Expressions of p53 and p21 were examined using Western blot analysis. RESULTS: The degree of apoptosis after heating in pH 6.6 medium was greater than in pH 7.5 medium in WERI cells. When heated in the same pH medium, more apoptosis occurred in the WERI cells than in the Y79 cells. The decline in cell viability caused by hyperthermia was greater than that by 50 mM of carboplatin in pH 6.6 medium but not in pH 7.5 medium. CONCLUSIONS: The cell death caused by the combination of carboplatin and hypethermia was greater than that by either treatment alone regardless of the environmental pH. It was concluded that an acidic environment enhances not carboplatin-induced cell death but heat-induced cell death.